Earlier experiments by William C. Rose (Nutr. Abst. Rev., 27, 631, 1957) demonstrated that a oral source of histidine was not needed for the maintenance of nitrogen balance in young, adult human subjects and was a non-essential amino acid for adult men. Later authors (cf., Irwin, M.I., and Hegsted D.M., J. Nutrition, 101, 539, 1971, and others) have questioned the conclusion that histidine was non-essential. In this connection, a rigorous, 72-day experiment has been completed wherein an adult human was maintained for 48 days with all amino acids being delivered by intravenous alimentation. A 3-day lysine-free intake caused a marked, negative nitrogen balance. Deletion of histidine led to a continued apparent mild positive nitrogen balance for 27 days. Many components, including 8 serum proteins, were constant throughout the 72 days. A decline in plasma and urinary histidine was observed during the histidine-devoid period. Many other tests of organ systems were performed. Administered 15NH4Cl was incorporated into the histidine isolated from hemoglobin. These results have been accepted for journal publication. The focus of this project is to ascertain the role of histidine in selected animals and to clarify the implied pathway of formation. Further specific experiments to clarify the above interrelationships and some ambiguities by use of radioisotope 14C studies are proposed. These and other findings must be considered in the evaluation of the essentiality of histidine for normal man and specified animals.